Nutritional and Hormonal Regulation of the Activity State of Hepatic Branched‐Chain α‐Keto Acid Dehydrogenase Complex

ROBERT A. HARRIS, GARY W. GOODWIN, RALPH PAXTON, PAUL DEXTER, STEVEN M. POWELL, BEI ZHANG, AMY HAN, YOSHIHARU SHIMOMURA, REID GIBSON

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14 Scopus citations

Abstract

The hepatic branched-chain α-keto acid dehydrogenase complex plays an important role in regulating branched-chain amino acid levels. These compounds are essential for protein synthesis but are toxic if present in excess. When dietary protein is deficient, the hepatic enzyme is present in the inactive, phosphorylated state to allow conservation of branched-chain amino acids for protein synthesis. When dietary protein is excessive, the enzyme is in the active, dephosphorylated state to commit the excess branched-chain amino acids to degradation. Inhibition of protein synthesis by cycloheximide, even when the animal is starving for protein, results in activation of the hepatic branched-chain α-keto acid dehydrogenase complex to prevent accumulation of branched-chain amino acids. Likewise, the increase in branched-chain amino acids caused by body wasting during starvation and uncontrolled diabetes is blunted by activation of the hepatic branched-chain α-keto acid dehydrogenase complex. The activity state of the hepatic branched-chain α-keto acid dehydrogenase complex is regulated in the short term by the concentration of branched-chain α-keto acids (inhibitors of branched-chain α-keto acid dehydrogenase kinase) and in the long term by alteration in the total branched chain α-keto acid dehydrogenase kinase activity.

Original languageEnglish (US)
Pages (from-to)306-313
Number of pages8
JournalAnnals of the New York Academy of Sciences
Volume573
Issue number1
DOIs
StatePublished - Dec 1989

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • History and Philosophy of Science

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